The cardio-cerebrovascular diseases are the most serious disorders currently endangering human life and health, which are common and frequent for the middle-aged and elderly people. In many countries, they are at the top in morbidity and mortality. Atherosclerosis contributes to a number of cardio-cerebrovascular diseases, and there are substantial evidences in laboratory and clinical data that atherosclerosis is closely associated with abnormal metabolism of blood lipid. Therefore, the medicaments for adjusting blood lipid represent an important field of current study on new medicament.
By forward, randomized and control clinical studies, it has been established that some statins enable reduced occurrence of atherosclerosis and coronary disease, lowering mortality caused by coronary disease and lowering incidence of myocardial infarction. Moreover, it has been further established that treatment with lipid-lowering drugs enables reduced lipid in atherosclerotic plaque and reinforced fiber lipid for stabilization of the plaque, leading to reduction of such severe events as myocardial infarction and cerebral infarction caused by plaque fracture. In addition, the medicaments for regulating blood lipid also enable the functions of the damaged vascular endotheliocyte to resume, enhance fibrinolysis, prevent thrombosis, and delay progression of atherosclerosis in human and remove the formed plaque. Therefore, it is an important approach for positive treatment with the blood lipid-regulating medicaments to reduce occurrence of atherosclerosis and coronary disease.
There are a variety of clinic and common medicaments for regulating blood lipid, for example HMG-CoA reductase inhibitors, phenoxy carboxylic acids, ion exchange resins orbile acid sequestrants, niacins and others. Among others, the statins (i.e. HMG-CoA reductase inhibitors) are particularly attractive.
The statins are the inhibitors of cholesterol synthetase. For conversion of HMG-CoA into mevalonic acid by the HMG-CoA reductase, the statins have an open acid moiety in the chemical structure similar as HMG-CoA, which is capable of competitively inhibiting formation of mevalonic acid, thus reducing synthesis of cholesterol, resulting in reduction of cholesterol and low-density lipoprotein (LDL-C) level in blood. There are further clinical studies showing that, in the patients with coronary disease even in which the cholesterol and low-density lipoprotein levels in sera are less high or normal, the stains are also capable of preventing occurrence, development of atherosclerotic plaque and reducing the severe clinic events such as coronary disease. However, for long-term dosing with the statins, in most of patients, impaired liver function, increased aminotransferases, muscular pain and increased creatine kinases will occur, in addition to such symptoms in digestive system as epigastric discomfort.
Therefore, there is an objective demand for constant development of new lipid-lowering drug with good efficacy and low side effects.